1. Field of the Invention
The present invention relates generally to the field of medical devices and medicine. More particularly, it concerns antimicrobial catheters with improved antimicrobial and physical properties.
2. Description of Related Art
Vascular catheters are important life saving devices with widespread use. They provide direct, immediate access to the bloodstream for a variety of critical purposes including transfusions, administering medications, nutrition, blood sampling for testing, and cardiac pressure and output monitoring. Catheters with multiple lumens are often used to meet these different needs.
Although catheters can provide many benefits, a significant risk of infection remains. Because vascular catheters provide access across surfaces that are ordinarily sealed from external environments, they can serve as conduits for pathogenic micro-organisms to colonize catheter surfaces and gain access to the bloodstream. Potential complications include bacteremia and bloodstream infection. Catheter associated blood stream infections can be costly to treat and may also result in significant adverse effects including mortality. Antimicrobial catheters incorporate antimicrobial agents to prevent infections. The clinical benefits of specific antimicrobial catheters have been shown, and Minocycline/Rifampin and Chlorhexidine/Silver Sulfadiazine catheters have recently been accorded the highest level recommendation for use by the Center for Disease Control (CDC) committee on Central Line Associated Blood Stream Infections (CLABSIs). The organisms causing CLABSIs are consistently shifting in prevalence. Over the last decade the reported relative incidence of infection by Candidemia, Enterococcal, and gram negative organisms has increased. Accordingly, improved antimicrobial agent combinations are needed to respond to these new threats. Chlorhexidine has been combined with Minocycline and Rifampin (CH/M/R) to give broader spectrum protection. In other instances, the combination of chlorhexidine with triarylmethane dyes such as Gentian Violet (gendine) or Brilliant Green (gardine) have been used to provide improved antimicrobial protection.
The improvements in antimicrobial protection associated with CH/M/R and Gendine/Gardine combinations have lead to some undesirable complications or costs. As shown herein, one such complication is that the processes needed to incorporate these agents into vascular catheters can result in catheters that can display undesirable mechanical properties. Stiff catheters are generally required to withstand the solvents and penetrating agents required for impregnation of the antimicrobial agents. Residual stiffness in the catheters can irritate and inflame the blood vessels they reside within. This irritation is frequently a result of mechanical stress exerted by the catheter on the vessel wall. If the catheter is present in a vein, this can lead to phlebitis, stenosis, and/or thrombus formation. Other mechanical complications may also be associated with the function of catheters. In curved vessels, the bending of stiff or inelastic catheters can kink, causing lumens to seal under aspiration or have reduced cross-sectional area. As further shown herein, the introduction of several antimicrobial agents in combination can also create physical and chemical stability challenges associated with long-term storage. Antimicrobial agents may migrate over time to surfaces creating roughness or rapid release of the antimicrobial agents. Thrombus can also form on the catheter due to thrombin or platelet activation, which can occlude lumens. Methods involved with impregnating additional antimicrobial agents can raise the costs associated with making and packaging antimicrobial catheters to economically unattractive levels. Clearly, there remains a need for antimicrobial catheters with improved physical properties.